P-gp inhibitor 1

P-gp inhibitor 1 is a novel inhibitor reversing P-glycoprotein-mediated multidrug resistance.

Research Areas >> Cancer

Signaling Pathways >> Membrane Transporter/Ion Channel >> P-glycoprotein

P-glycoprotein[1]

P-gp inhibitor 1 (12k) possesses high potency (EC50=57.9±3.5 nM), low cytotoxicity, and long duration of activity in reversing doxorubicin (DOX) resistance in K562/A02 cells (1 μM, 80 minutes)[1]. P-gp inhibitor 1 also boosts the potency of other MDR-related cytotoxic agents with different structures, increases accumulation of DOX, blocks Pgp-mediated Rh123 efflux, and suppresses P-gp ATPase activity in K562/A02 MDR cells (0.1, 1, 5 μM, 1 hour)[1]. Western Blot Analysis[1] Cell Line: K562/A02 cell Concentration: 0.1, 0.5, or 2.0 μM Incubation Time: 72 hours Result: MDR reversal by 12k was not caused by a decreased protein expression but instead most likely due to direct inhibition of P-gp efflux[1].

[1]. Qiu Q, et al. Design, Synthesis, and Pharmacological Characterization of N-(4-(2 (6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)yl)ethyl)phenyl)quinazolin-4-amine Derivatives: Novel Inhibitors Reversing P-Glycoprotein-Mediated Multidrug Resistance. J Med Chem. 2017 Apr 27;60(8):3289-3302.